Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019, 163(4):309-317 | DOI: 10.5507/bp.2018.054

Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates

Anna Chaloupkaa, Lenka Piherovab, Ilga Grochovaa, Jana Binovac, Jan Krejcia, Lenka Spinarovaa, Viktor Straneckyb, Stanislav Kmochb, Milos Kubanekc
a 1 st Internal Clinic of Cardio-angiology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
b Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, 1 st Faculty of Medicine, Charles University, Prague, Czech Republic
c Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Aims: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology and clinical outcome. In this pilot study, we aimed to assess its genetic architecture and correlate genotype with left ventricular reverse remodelling (LVRR).

Patients and Methods: In this multi-centre prospective observational study, we enrolled 83 Moravian patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing (WES). All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejection fraction > 10% accompanied by a relative decrease of left ventricular end-diastolic diameter > 10% at 12 months.

Results: WES identified at least one disease-related variant in 45 patients (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncated variants, followed by individuals with a negative, or inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs. 19%, P=0.041).

Conclusion: A substantial proportion of RODCM cases have a monogenic or oligogenic genetic background. Carriers of non-titin disease-related variants are less likely to reach LVRR at 12- months than other individuals. Genetic testing could contribute to better prognosis prediction and individualized treatment of RODCM.

Keywords: dilated cardiomyopathy, familial cardiomyopathy, next generation sequencing, genetic architecture, cardiac remodelling

Received: July 31, 2018; Accepted: September 7, 2018; Prepublished online: September 24, 2018; Published: December 11, 2019  Show citation

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Chaloupka, A., Piherova, L., Grochova, I., Binova, J., Krejci, J., Spinarova, L., ... Kubanek, M. (2019). Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates. Biomedical papers, 163(4), 309-317. doi: 10.5507/bp.2018.054
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